Can We Use Antibodies to Chlamydia trachomatis as a Surveillance Tool for National Trachoma Control Programs? Results from a District Survey

West, Sheila K.; Muñoz, Beatriz; Weaver, Jerusha; Mrango, Zakayo; Dize, Laura; Gaydos, Charlotte A.; Quinn, Thomas C.; Martin, Diana L.

doi:10.1371/journal.pntd.0004352

Cited by 46 publications

(65 citation statements)

References 10 publications

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“…By monitoring the exposure to Ct of the youngest age groups, born after implementation of MDA, serology may prove useful for confirming that transmission has been interrupted [22]. …”

Section: Introductionmentioning

confidence: 99%

“…Serology has recently been used in several studies [19,20,22–24], three of which have taken place in districts that have completed three or more rounds of MDA [22–24]. These studies have used the multiplex bead array platform (Bio-rad, Hercules, California) to detect antibodies against Pgp3 and CT694, antigens thought to be highly immunogenic [25].…”

Section: Introductionmentioning

confidence: 99%

“…These studies have used the multiplex bead array platform (Bio-rad, Hercules, California) to detect antibodies against Pgp3 and CT694, antigens thought to be highly immunogenic [25]. Because this platform is costly, technically complex and unlikely to be found in most laboratories in resource-limited regions, alternative, simpler methods of antibody detection have been proposed [22,26]. …”

Section: Introductionmentioning

confidence: 99%

“…To make serological testing more widely accessible, the Pgp3/CT694 assay used in previous studies [19,20,22–24] has been adapted for use in a simple Pgp3-specific enzyme-linked immunosorbent assay (ELISA). Pgp3 is a Ct-specific 84kDa heterotrimeric protein [27] and is recognised by specific IgG [28].…”

Section: Introductionmentioning

confidence: 99%

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Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies

et al. 2017

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BackgroundEfforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies.MethodologyDried blood spots were collected in 2014 from children aged 1–9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1–90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared.Principal FindingsSeroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden’s J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples.ConclusionsInternally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard.

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“…By monitoring the exposure to Ct of the youngest age groups, born after implementation of MDA, serology may prove useful for confirming that transmission has been interrupted [22]. …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies

et al. 2017

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“…Data from cross-sectional surveillance tools used in isolation can be hard to interpret, especially given the prolonged persistence of TF after clearance of infection 33 . Some features of conjunctivitis in the Solomon Islands resemble trachoma, particularly the prevalent follicular inflammation and some of the severe conjunctival scarring.…”

Section: Discussionmentioning

confidence: 99%

Clinical signs of trachoma are prevalent among Solomon Islanders who have no persistent markers of prior infection with Chlamydia trachomatis

Butcher¹,

Sokana²,

Jack³

et al. 2018

Wellcome Open Res

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Background: The low population-prevalence of trachomatous trichiasis and high prevalence of trachomatous inflammation–follicular (TF) provide contradictory estimates of the magnitude of the public health threat from trachoma in the Solomon Islands. Improved characterisation of the biology of trachoma in the region may support policy makers as they decide what interventions are required. Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring were examined to determine whether there is evidence of ongoing transmission and pathology from ocular Chlamydia trachomatis (Ct) infection. Methods: A total of 1511 individuals aged ≥1 year were enrolled from randomly selected households in 13 villages in which >10% of children aged 1–9 years had TF prior to a single round of azithromycin mass drug administration undertaken six months previously. Blood was collected to be screened for antibodies to the Ct antigen Pgp3. Tarsal conjunctival photographs were collected for analysis of scarring severity. Results: Anti-Pgp3 seropositivity was 18% in 1–9 year olds, sharply increasing around the age of sexual debut to reach 69% in those over 25 years. Anti-Pgp3 seropositivity did not increase significantly between the ages of 1–9 years and was not associated with TF (p=0.581) or scarring in children (p=0.472). Conjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not severe (p=0.149) scars increased in prevalence with age. Conclusions: Neither conjunctival scars nor lymphoid follicles were associated with antibodies to Ct, suggesting that they are unlikely to be a direct result of ocular Ct infection . Clinical signs of trachoma were prevalent in this population but were not indicative of the underlying rates of Ct infection. The current World Health Organization guidelines for trachoma elimination indicated that this population should receive intervention with mass distribution of antibiotics, but the data presented here suggest that this may not have been appropriate.

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Surveillance Surveys for Reemergent Trachoma in Formerly Endemic Districts in Nepal From 2 to 10 Years After Mass Drug Administration Cessation

West¹,

Zambrano²,

Sharma³

et al. 2017

JAMA Ophthalmol

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IMPORTANCETo verify districts for elimination of blinding trachoma, the World Health Organization requires a population-based surveillance survey for follicular trachoma (TF) and trachomatous trichiasis (TT) 2 years after mass drug administration (MDA) activities have ceased. However, it is unknown if 2 years provides enough time to discover reemergence.OBJECTIVE To determine the prevalence of trachoma from surveys among 4 districts in Nepal (Dailekh, Dang, Surkhet, and Kanchanpur) that had surveillance intervals of 2, 4, 8, and 10 years, respectively, after cessation of MDA. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional surveys were carried out in 2015 and 2016. Data analyses were done from March to September 2016. Among 20 clusters randomly selected from each district, 15 were randomly selected for infection and antibody testing: TF and TT were assessed, conjunctival swabs were tested for chlamydial infection, and blood spots were collected on filter paper to test for antibodies to Chlamydia trachomatis pgp3 using a multiplex bead assay. The study setting was 4 districts previously endemic for trachoma in Nepal. Participants were randomly selected and included 50 children aged 1 to 9 years and 100 adolescents and adults 15 years and older from each of the 20 clusters; this investigation reports on the children. MAIN OUTCOMES AND MEASURESLength of time since the last round of MDA and the prevalence of TF among children aged 1 to 9 years and the prevalence of TT among adolescents and adults 15 years and older. RESULTSOf 3024 children surveyed in the clusters, 48.0% (n = 1452) were female. The mean (SD) age of the children was 5.4 (2.6) years. Eleven cases of TF were found, with a TF prevalence less than 1% in all 4 districts. Three cases of infection were found. Seropositivity for pgp3 antibody varied from 1.4% (95% CI, 0.7-2.6) in the district with a 10-year surveillance interval to 2.5% (95% CI, 1.3-4.5) in the district with a 4-year surveillance interval. Seropositivity increased slightly with age in only one district. The TT prevalence was less than 1 case per 1000 among the total population in all 4 districts after accounting for cases known to the health system and cases with no scarred conjunctiva. CONCLUSIONS AND RELEVANCEThis study found no evidence of reemergence of trachoma up to 10 years after cessation of MDA in 4 districts in children in Nepal. The recommendation for a surveillance survey at 2 years, as proposed by the World Health Organization, is supported by these data. Determining if individuals with TT had scarring or are known to the health system was critical for meeting elimination criteria of blinding trachoma.

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Can We Use Antibodies to Chlamydia trachomatis as a Surveillance Tool for National Trachoma Control Programs? Results from a District Survey

Cited by 46 publications

References 10 publications

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies

Clinical signs of trachoma are prevalent among Solomon Islanders who have no persistent markers of prior infection with Chlamydia trachomatis

Surveillance Surveys for Reemergent Trachoma in Formerly Endemic Districts in Nepal From 2 to 10 Years After Mass Drug Administration Cessation

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